1. Field of the Invention
This invention relates to the direct treatment of injured mammalian tissue, for example, abraded, lacerated or ulcerated tissues, through the use of a topical ointment composition which has the capacity of adjusting the acid-base balance of the area to which the composition is applied to a point where healing from within can take place.
2. Prior Observations
The skin, supporting body tissues, connective tissues and viscera are subject to a variety of irritations, infections and injuries. These often result in the disruption of the continuity, configuration and appearance of normal tissues and may appear as areas of ulceration, necrosis, contusion, laceration, inflammation and tumefaction. Conventional compositions for dressings to be applied to such irritated or injured tissues often act as foreign bodies and are frequently themselves a source of irritation which may impede the healing process and promote infection.
The skin is composed of two layers, i.e., the epidermis or cuticle and the dermis or true skin. The epidermis is a thin outer layer composed of stratified epithelium. The cells in the deepest portion of the epidermis, the Malpighian layer, multiply and, in growing, push the older cells of the epidermis upward toward the surface. As these cells move upwardly they become flattened and plate-like in shape. The epidermis, being generally devoid of blood vessels, is dependent for its nutrition upon the vessels found in the dermis. These vessels end as capilliary loops in the papillae of the dermis. The more superficial cells of the epidermis, being far removed from the nutrient supply, gradually degenerate and their proteins are transformed into keratin. This process, termed keratinization, results in the death of the cells. Keratin is the most insoluble of all proteinaceous material which gives the upper layer of the skin (the stratum corneum) a horn like consistency. During the life process, the outermost dead scales of keratin are gradually shed and replaced by more recently keratinized cells. Keratin also is found in the appendages of the skin, that is, in the nails and hair. In the lower animals it is found in the horns, hoofs and claws. In the palms of the hands and soles of the feet, the epidermis is much thicker than elsewhere.
The true skin, corium or dermis, lies just below the Malpighian layer and is formed of loose connective tissue which sends little elevations known as papillae into the cuticle or epidermis. At its deepest portions the dermis gradually passes into the areolar subcutaneous tissue. In the dermis, or more especially, in the subcutaneous tissue, a variable amount of adipose tissue exists. While the epidermis is not supplied with blood vessels, the dermis is very vascular and the sebaceous (oil) and sudoriferous (sweat) glands are located in the dermis. The oil glands, which reside in the deeper parts of the skin, are distributed in all areas of the body except the soles of the feet and the palms of the hands. The sebaceous secretion, known as sebum, contains fats, proteins, water, salt, and remnants of epithelial cells. The sebum protects the structures of the skin and the hair against intolerable drying and breakage by oiling the same and thus the physical integrity of the skin is preserved. Additionally, the sebum prevents excessive loss of water by the skin.
One of the primary functions of the skin is protection. The epidermis of the skin, which is composed of hard, resistant cells, forms the bodies first line of defense against mechanical and chemical injuries and, above all, against bacterial invasion, because the unbroken skin is substantially germ proof. This protection is evidenced by the frequent infections which occur when the skin is injured so as to expose the underlying tissues. Recently, it has been demonstrated that the skin not only serves as a mechanical barrier but that it also possesses immunizing powers. Additionally, the sense organs for heat and cold, touch and pain are located in the dermis. Further, the skin helps to regulate body temperature through vasomotor reactions of blood vessels and through evaporation of perspiration. Perspiration sometimes has acidic and sometimes basic properties and its odor may be very marked and differs in various regions of the body. The skin also plays an important part in water metabolism, calcium metabolism and to a lesser degree, excretion and adsorption.
Various injuries which effect the skin include those caused by allergic reactions, mechanical impact or abrasion, chemical attack, heat, etc. These may result in disruption of normal tissue continuity, configuration and appearance and may appear as areas of ulceration, necrosis, contusion, laceration, inflammation and tumefaction.
The terms above, for the purposes of this specification, are intended to have the following meanings:
Ulcer -- is a local defect or excavation of the surfaces of an organ produced by sloughing of necrotic inflammatory tissue;
Decubitus ulcer -- is an ulceration caused by prolonged pressure on a body area in a patient confined to bed;
Necrosis -- is the death of a cell as a result of a disease or injury;
Contusion -- is an injury to tissues without breakage of the skin;
Laceration -- is a wound produced by tearing;
Inflammation -- is a specific tissue response to injury by living agents, or to electrical, chemical or mechanical trauma, evidenced by vascular dilatation, fluid exudation, or accumulation of lukocytes or any combination of the three;
Tumefaction -- is a swelling or puffiness;
Rash -- is a temporary erruption on the skin;
Diaper Rash -- is a dermatitis of the gluteal region of infants.
Erythema -- is a congestive or exudative redness of the skin caused by hyperima which is an excess of blood in a particular part;
Edema -- is an abnormal accumulation of fluid in the intracellular spaces of the body;
Eczema -- is generally a skin disease having associated therewith, itching and redness.
Various compositions useful for treatment of injuries to the skin are known in the prior art. Among these known compositions are the following:
Furacin (a registered trademark of Eaton Laboratory, Norwich, New York) is a topical cream containing nitrofurazone in a base consisting of glycerine, cetyl alcohol, mineral oil, an ethoxylated fatty alcohol, methylparaben, propylparaben and water. The water miscible base is self-emulsifying in various body fluids. The topical cream finds use in the treatment or prophylaxis of the surface bacterial infections.
Elase Ointment (a registered trademark of the Parke-Davis Company, Detroit, Michigan) is a combination of two lytic enzymes, fibrinolysin and desoxyribonuclease, in an ointment. The fibrinolysin component is derived from bovine plasma and the desoxyribonuclease is isolated in a purified form from bovine pancreas. The combination of these two enzymes is based on the observation that purulent exudates consist largely of fibrinous material and nucleoprotein. Desoxyribonuclease attacks the desoxyribonucleic acid (DNA) and fibrinolysin attacks principally fibrin of blood clots and fibrinous exudates. Elase is used topically as a debriding agent in a variety of inflammatory and infected lesions including (1) general surgical wounds, (2) ulcerative lesions, i.e., trophic, decubitus, stasis, arteriosclerotic; and (3) second and third degree burns.
Oxylone (a registered trademark of the Upjohn Company, Kalamazoo, Michigan) contains fluorometholone, which is a steroid, in addition to glyceryl monostearate, spermaceti, polyethylene glycol emulsifier, water and preservatives. This material includes a water soluble vanishing cream base designed for use on exposed regions of the skin such as the face and hands and is allegedly effective because of the anti-inflammatory, anti-pruritic and vasoconstrictive action provided by the steroid, fluorometholone. The cream is used to obtain symptomatic relief and adjunctive management of various dermatoses including sunburn, eczema and diaper rash.
Mycolog (a registered trademark of E. R. Squibb & Sons, Princeton, New Jersey) is a dermatologic preparation used in cases of dermatitis complicated with a superficial bacterial infection. Among other things, it is anti-fungal and anti-bacterial and contains nystatin, neomycin sulfate, gramicidin, and triamcinolone acetonide either in a vanishing cream base or in a protective base of polyethylene and mineral oil gel.
Neosporin (a registered trademark of the Burroughs-Wellcome Company, North Carolina) provides anti-bacterial action against commonly occuring bacteria known to be topical invaders. The ointment contains neomycin sulfate, zinc bacitracin and polymyxin B-sulfate.
The foregoing compositions, even though many of the same include fungicides, bacteriacides or hazardous steroids, still do not provide either the degree or speed of healing which is obtained with the composition of the instant invention in the treatment of many injuries to the skin, as will be clearly shown in the examples infra.